(Anglais) The research in the field of contrast agent for magnetic resonance imaging focuses nowadays on the development of specific compounds for molecular imaging.
To this end, part of our research deals with the elaboration of gadolinium agents interacting with human serum albumin (HSA). Indeed, when a paramagnetic complex has some affinity for HSA, his effect on water protons magnetic relaxation is improved and his vascular remanence is increased. The efficacy of the complex therefore increases and its use in angiography becomes possible.
Various techniques, like ultrafiltration [1], mass spectrometry [2], and NMR spectroscopy [3] have proved their efficacy for measuring this type of non covalent binding. We have used here a technique, called NMR diffusometry, which consists in the study of the variation of the ligand diffusion coefficient in the absence and in the presence of HSA.
One problem of this method, well known in the literature, is the presence of the background of the HSA signals, hiding the peaks of interest. To avoid this, we decided to work with europium complexes since this lanthanide is well knowm for being able to shift the signals outside the HSA’s background.
In order to test the feasibility of the technique, we have studied three Europium complexes : two well-known in the literature for their interaction with HSA, Eu-EOB-DTPA and Eu-MP2269, and one, Eu-DTPA, which does not exhibit significant affinity for the protein. The results confirm the extremely weak interaction of Eu-DTPA with HSA and a more important affinity of Eu-EOB-DTPA. Interestingly, this technique does not allow to study Eu-MP2269 because of its slow exchange with HSA.
[1] Caravan P., Cloutier N.J., Greenfield M.T., McDermid S.A., Dunham S.U., Bulte J.W.M., Amedio J.C., Looby R.J., Supkowski R.M., Horrocks W.D., McMurry T.J., Lauffer R.B., « The interaction of MS-325 with Human Serum Albumin and Its Effect on Proton Relaxation Rates », J.Am.Chem.Soc. 124 (12) 3152-3162 (2002)
[2] Henrotte V., Laurent S., Gabelica V., Vander Elst L., De Pauw E., Muller RN., « Investigation of non-covalent interactions between paramagnetic complexes and human serum albumin by electrospray mass spectrometry », Rap. Comm. Mass Spectrom. 18 (17): 1919-1924 (2004)
[3] Lepre C.A., Moore J.M., Peng J.W., « Theory and Applications of NMR-Based Screening in Pharmaceutical Research », Chem. Rev., 104, 3641-3675 (2004)